While the cholinergic depletion in Alzheimer's disease (AD) has been known for some time, a definitive involvement of other neurotransmitter systems has been somewhat more elusive. Our study demonstrates a clear involvement of both glutamatergic and, to a lesser extent, GABAergic neurons in an early onset transgenic mouse model of AD-like amyloid pathology. Immunohistochemical staining and subsequent quantification has revealed a statistically significant increased density of glutamatergic and GABAergic presynaptic boutons in both the plaque free and plaque adjacent cortical neuropile areas of transgenic mice as compared to non-transgenic controls. Furthermore, amyloid plaque size was shown to have a statistically significant effect on the relative area occupied by dystrophic glutamatergic neurites in the peri-plaque neuropile. These findings support our hypothesis that the amyloid pathology progresses in a time and neurotransmitter specific manner, first in the cholinergic system which appears to be most vulnerable, followed by the glutamatergic presynaptic boutons and finally the somewhat more resilient GABAergic terminals.